Optimal sequencing of brain radiotherapy and immunotherapy for patients with non-small cell lung cancer and driver gene-negative, asymptomatic brain metastases.

[BACKGROUND] To investigate the efficacy and safety of combining brain radiotherapy (RT) with immune checkpoint inhibitors (ICIs) across different treatment sequences.

[MATERIALS AND METHODS] A retrospective analysis was performed on 95 patients with non-small cell lung cancer (NSCLC) characterized by negative driver genes and asymptomatic brain metastases (BM) who received ICIs. Patients were divided into three groups based on their receipt of brain RT and the timing relative to ICIs administration: group A (concurrent ICIs and RT), group B (sequential ICIs and RT), and group C (ICIs without RT). The efficacy and safety profiles of each group were assessed.

[RESULTS] The median follow-up time was 20 months (range: 2–57 months). The median intracranial progression-free survival (miPFS) for groups A, B, and C was 14 (95% CI: 9.139–18.861), 14 (95% CI: 9.213–18.787), and 10 months (95% CI: 5.213–14.787), respectively ( = 0.048). The median overall survival (mOS) for groups A, B, and C was 23 (95% CI: 18.489–27.511), 20 (95% CI: 15.186–24.814), and 15 months (95% CI: 10.390–19.610), respectively ( = 0.076). The incidence rates of RT-induced brain injury in groups A and B were 30.0% and 26.7%, respectively. Univariate and multivariate analyses identified combined bevacizumab treatment and high PD-L1 expression as independent favorable prognostic factors for OS.

[CONCLUSION] Among patients with NSCLC with negative driver genes and asymptomatic BM, combining ICIs with brain RT demonstrated superior efficacy compared with ICIs alone. Concurrent administration of ICIs and brain RT resulted in prolonged OS compared with sequential treatment, although the difference did not reach statistical significance, and the concurrent approach did not increase the risk of adverse events (AEs).